Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy loss

Abstract

Objective: To assess the effectiveness of luteal start vaginal micronized P in a recurrent pregnancy loss (RPL) cohort.

Design: Observational cohort study using prospectively collected data.

Setting: Not applicable.

Patient(s): Women seen between 2004 and 2012 with a history of two or more unexplained pregnancy losses <10 weeks in size; endometrial biopsy (EB) performed 9-11 days after LH surge; and one or more subsequent pregnancy(ies). Women were excluded if concomitant findings, such as endometritis, maturation delay, or glandular-stromal dyssynchrony, were identified on EB.

Intervention(s): Vaginal micronized P was prescribed at a dose of 100-200 mg every 12 hours starting 3 days after LH surge (luteal start) if glandular epithelial nuclear cyclin E (nCyclinE) expression was elevated (>20%) in endometrial glands or empirically despite normal nCyclinE (≤20%). Women with normal nCyclinE (≤20%) who did not receive P were used as controls.

Main outcome measure(s): Pregnancy success was an ongoing pregnancy >10 weeks in size.

Result(s): One hundred sixteen women met the inclusion criteria, of whom 51% (n = 59) had elevated nCyclinE and 49% (n = 57) had normal nCyclinE. Pregnancy success in the 59 women with elevated nCyclinE significantly improved after intervention: 6% (16/255) in prior pregnancies versus 69% (57/83) in subsequent pregnancies. Pregnancy success in subsequent pregnancies was higher in women prescribed vaginal micronized P compared with controls: 68% (86/126) versus 51% (19/37); odds ratio = 2.1 (95% confidence interval, 1.0-4.4).

Conclusion(s): In this study, we found that the use of luteal start vaginal micronized P was associated with improved pregnancy success in a strictly defined cohort of women with RPL.

Keywords: Recurrent pregnancy loss; cyclin E; endometrium; progesterone; recurrent miscarriage.